A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer

Sebastian, Martin; Schröder, Andreas; Scheel, Birgit; Hong, Henoch S.; Muth, Anke; Boehmer, Lotta von; Zippelius, Alfred; Mayer, Frank; Reck, Martin; Atanackovic, Djordje; Thomas, Michael; Schneller, Folker; Stöhlmacher, J.; Bernhard, Helga; Gröschel, A.; Lander, T.; Probst, Jochen; Strack, Tanja; Wiegand, V.; Gnad-Vogt, Ulrike; Kallen, Karl-Josef; Hoerr, Ingmar; Muelbe, Florian von der; Fotin‐Mleczek, Mariola; Knuth, Alexander; Koch, Sven D.

doi:10.1007/s00262-019-02315-x

Cited by 133 publications

(126 citation statements)

References 51 publications

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“…Alternatively, RNA-based vaccines use mRNA that upon entering cells, are translated to antigenic molecules that in turn, stimulate the immune system. This process has been used effectively against some cancers [79,80], and clinical trials are underway for several other cancers [81]. In addition, the production of RNA-based vaccines is more rapid and less expensive than traditional vaccines, which can be a major advantage in pandemic situations.…”

Section: Vaccine Developmentmentioning

confidence: 99%

SARS-CoV-2 and Coronavirus Disease 2019: What We Know So Far

et al. 2020

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In December 2019, a cluster of fatal pneumonia cases presented in Wuhan, China. They were caused by a previously unknown coronavirus. All patients had been associated with the Wuhan Wholefood market, where seafood and live animals are sold. The virus spread rapidly and public health authorities in China initiated a containment effort. However, by that time, travelers had carried the virus to many countries, sparking memories of the previous coronavirus epidemics, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and causing widespread media attention and panic. Based on clinical criteria and available serological and molecular information, the new disease was called coronavirus disease of 2019 , and the novel coronavirus was called SARS Coronavirus-2 (SARS-CoV-2), emphasizing its close relationship to the 2002 SARS virus (SARS-CoV). The scientific community raced to uncover the origin of the virus, understand the pathogenesis of the disease, develop treatment options, define the risk factors, and work on vaccine development. Here we present a summary of current knowledge regarding the novel coronavirus and the disease it causes.

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Section: Vaccine Developmentmentioning

confidence: 99%

SARS-CoV-2 and Coronavirus Disease 2019: What We Know So Far

et al. 2020

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“…Protamine-based formulations for IVT mRNA delivery are the second most used chemical systems in clinical trials, although far from lipidic systems. RNActive ® technology, developed by CureVac, is an mRNA vaccine platform based on protamine/mRNA complexes currently under clinical evaluation against rabies [138], and different cancers [141,142]. RNActive ® platform also has been tested preclinically against the influenza virus infection [143].…”

Section: Polypeptidic Systemsmentioning

confidence: 99%

Nanomedicines to Deliver mRNA: State of the Art and Future Perspectives

et al. 2020

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The use of messenger RNA (mRNA) in gene therapy is increasing in recent years, due to its unique features compared to plasmid DNA: Transient expression, no need to enter into the nucleus and no risk of insertional mutagenesis. Nevertheless, the clinical application of mRNA as a therapeutic tool is limited by its instability and ability to activate immune responses; hence, mRNA chemical modifications together with the design of suitable vehicles result essential. This manuscript includes a revision of the strategies employed to enhance in vitro transcribed (IVT) mRNA functionality and efficacy, including the optimization of its stability and translational efficiency, as well as the regulation of its immunostimulatory properties. An overview of the nanosystems designed to protect the mRNA and to overcome the intra and extracellular barriers for successful delivery is also included. Finally, the present and future applications of mRNA nanomedicines for immunization against infectious diseases and cancer, protein replacement, gene editing, and regenerative medicine are highlighted.

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“…Despite their advantages, nucleic acid‐based vaccines have not been reliably effective in humans. Several vaccines have had disappointing clinical trials with only a small fraction of patients developing T‐cell responses against target antigens 62,90,91 . These trials tested numerous tumor‐associated antigens in several cancer types including renal cell carcinoma, non–small‐cell lung cancer, and melanoma.…”

Section: Vaccine Designmentioning

confidence: 99%

Polyomavirus‐driven Merkel cell carcinoma: Prospects for therapeutic vaccine development

Tabachnick-Cherny

Pulliam

Church

et al. 2020

Molecular Carcinogenesis

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Great strides have been made in cancer immunotherapy including the breakthrough successes of anti-PD-(L)1 checkpoint inhibitors. In Merkel cell carcinoma (MCC), a rare and aggressive skin cancer, PD-(L)1 blockade is highly effective. Yet,~50% of patients either do not respond to therapy or develop PD-(L)1 refractory disease and, thus, do not experience long-term benefit. For these patients, additional or combination therapies are needed to augment immune responses that target and eliminate cancer cells. Therapeutic vaccines targeting tumor-associated antigens, mutated self-antigens, or immunogenic viral oncoproteins are currently being developed to augment T-cell responses. Approximately 80% of MCC cases in the United States are driven by the ongoing expression of viral T-antigen (T-Ag) oncoproteins from genomically integrated Merkel cell polyomavirus (MCPyV). Since T-Ag elicits specific B-and T-cell immune responses in most persons with virus-positive MCC (VP-MCC), and ongoing T-Ag expression is required to drive VP-MCC cell proliferation, therapeutic vaccination with T-Ag is a rational potential component of immunotherapy. Failure of the endogenous T-cell response to clear VP-MCC (allowing clinically evident tumors to arise) implies that therapeutic vaccination will need to be potent anśd synergize with other mechanisms to enhance T-cell activity against tumor cells. Here, we review the relevant underlying biology of VP-MCC, potentially applicable therapeutic vaccine platforms, and antigen delivery formats. We also describe early successes in the field of therapeutic cancer vaccines and address several clinical scenarios in which VP-MCC patients could potentially benefit from a therapeutic vaccine. K E Y W O R D S cancer therapeutic vaccine, immunotherapy, MCPyV, Merkel cell carcinoma

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A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer

Cited by 133 publications

References 51 publications

SARS-CoV-2 and Coronavirus Disease 2019: What We Know So Far

SARS-CoV-2 and Coronavirus Disease 2019: What We Know So Far

Nanomedicines to Deliver mRNA: State of the Art and Future Perspectives

Polyomavirus‐driven Merkel cell carcinoma: Prospects for therapeutic vaccine development

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